JPS5823877B2 - ナフチリジン誘導体およびその製造方法 - Google Patents
ナフチリジン誘導体およびその製造方法Info
- Publication number
- JPS5823877B2 JPS5823877B2 JP52041904A JP4190477A JPS5823877B2 JP S5823877 B2 JPS5823877 B2 JP S5823877B2 JP 52041904 A JP52041904 A JP 52041904A JP 4190477 A JP4190477 A JP 4190477A JP S5823877 B2 JPS5823877 B2 JP S5823877B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- compounds
- hydrogen atom
- indolo
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 150000005054 naphthyridines Chemical class 0.000 title claims 4
- 238000004519 manufacturing process Methods 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 43
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 30
- -1 3-oxo-butyl group Chemical group 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 230000003287 optical effect Effects 0.000 claims description 4
- 150000007522 mineralic acids Chemical class 0.000 claims 3
- 150000007524 organic acids Chemical class 0.000 claims 3
- 229940079593 drug Drugs 0.000 claims 1
- 229940001470 psychoactive drug Drugs 0.000 claims 1
- 239000004089 psychotropic agent Substances 0.000 claims 1
- 238000000034 method Methods 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 238000002844 melting Methods 0.000 description 20
- 230000008018 melting Effects 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 239000000203 mixture Substances 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- QPYPBNRHDGXJMA-UHFFFAOYSA-N 4h-1,8-naphthyridin-3-one Chemical compound C1=CN=C2N=CC(=O)CC2=C1 QPYPBNRHDGXJMA-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 125000004430 oxygen atom Chemical group O* 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- VMLKTERJLVWEJJ-UHFFFAOYSA-N 1,5-naphthyridine Chemical class C1=CC=NC2=CC=CN=C21 VMLKTERJLVWEJJ-UHFFFAOYSA-N 0.000 description 3
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical group N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical group NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- 125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 230000001054 cortical effect Effects 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- 235000019256 formaldehyde Nutrition 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 231100000636 lethal dose Toxicity 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000003368 psychostimulant agent Substances 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 230000007958 sleep Effects 0.000 description 2
- 230000004617 sleep duration Effects 0.000 description 2
- 230000004622 sleep time Effects 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- GXFZCDMWGMFGFL-KKXMJGKMSA-N (+)-Tubocurarine chloride hydrochloride Chemical compound [Cl-].[Cl-].C([C@H]1[N+](C)(C)CCC=2C=C(C(=C(OC3=CC=C(C=C3)C[C@H]3C=4C=C(C(=CC=4CC[NH+]3C)OC)O3)C=21)O)OC)C1=CC=C(O)C3=C1 GXFZCDMWGMFGFL-KKXMJGKMSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- HQMKWWYYKCFZJF-UHFFFAOYSA-N 1,5-naphthyridine-4-carboxylic acid Chemical compound C1=CN=C2C(C(=O)O)=CC=NC2=C1 HQMKWWYYKCFZJF-UHFFFAOYSA-N 0.000 description 1
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- OJFSCKNLUYOABN-UHFFFAOYSA-N 1h-1,5-naphthyridin-2-one Chemical compound N1=CC=CC2=NC(O)=CC=C21 OJFSCKNLUYOABN-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- PYNYHMRMZOGVML-UHFFFAOYSA-N 2-bromopropanenitrile Chemical compound CC(Br)C#N PYNYHMRMZOGVML-UHFFFAOYSA-N 0.000 description 1
- YSHMADXLRZITGF-UHFFFAOYSA-N 3-methyl-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole Chemical compound N1C2=CC=CC=C2C2=C1CNC(C)C2 YSHMADXLRZITGF-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 241001111317 Chondrodendron tomentosum Species 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- 241000252095 Congridae Species 0.000 description 1
- 239000008709 Curare Substances 0.000 description 1
- 101100440695 Dictyostelium discoideum corB gene Proteins 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 230000000496 anti-anoxic effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 229940082992 antihypertensives mao inhibitors Drugs 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000004803 chlorobenzyl group Chemical group 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- FDSGHYHRLSWSLQ-UHFFFAOYSA-N dichloromethane;propan-2-one Chemical compound ClCCl.CC(C)=O FDSGHYHRLSWSLQ-UHFFFAOYSA-N 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- LHHLYOVYBZWIGM-UHFFFAOYSA-N diethyl 2-formylbutanedioate Chemical compound CCOC(=O)CC(C=O)C(=O)OCC LHHLYOVYBZWIGM-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000004175 fluorobenzyl group Chemical group 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
- 229960004801 imipramine Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- VBEHBFWLIMJNIN-UHFFFAOYSA-N methyl 12-fluoro-2-oxo-1,6-diazatetracyclo[7.6.1.05,16.010,15]hexadeca-9(16),10,12,14-tetraene-4-carboxylate Chemical compound C12=CC(F)=CC=C2N2C(=O)CC(C(=O)OC)C3C2=C1CCN3 VBEHBFWLIMJNIN-UHFFFAOYSA-N 0.000 description 1
- XPRGOYLRHUGZPZ-UHFFFAOYSA-N methyl 2-oxo-1,6-diazatetracyclo[7.6.1.05,16.010,15]hexadeca-9(16),10,12,14-tetraene-4-carboxylate Chemical compound C12=CC=CC=C2N2C(=O)CC(C(=O)OC)C3C2=C1CCN3 XPRGOYLRHUGZPZ-UHFFFAOYSA-N 0.000 description 1
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 102200083966 rs80358212 Human genes 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 208000009999 tuberous sclerosis Diseases 0.000 description 1
- 229940072358 xylocaine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Cardiology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7610773A FR2358146A1 (fr) | 1976-04-13 | 1976-04-13 | Derives de la tetrahydro-1,2,3,3a indolo(3,2,1-de) (1,5)naphtyridine |
| FR7616445A FR2353550A2 (fr) | 1976-06-01 | 1976-06-01 | Procede de preparation de derives de naphtyridine |
| FR7632319A FR2368955A2 (fr) | 1976-10-27 | 1976-10-27 | Derives de la tetrahydro-1,2,3,3a indolo (3,2,1-de) (1,5) naphtyridine |
| FR7639035A FR2374905A2 (fr) | 1976-12-24 | 1976-12-24 | Derives de naphtyridine |
| FR7707249A FR2383182A2 (fr) | 1977-03-11 | 1977-03-11 | Nouveaux derives de naphtyridine |
| FR7707248A FR2383181A2 (fr) | 1977-03-11 | 1977-03-11 | Derives de naphtyridine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS52125198A JPS52125198A (en) | 1977-10-20 |
| JPS5823877B2 true JPS5823877B2 (ja) | 1983-05-18 |
Family
ID=27546337
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP52041904A Expired JPS5823877B2 (ja) | 1976-04-13 | 1977-04-11 | ナフチリジン誘導体およびその製造方法 |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US4190657A (en:Method) |
| JP (1) | JPS5823877B2 (en:Method) |
| AR (1) | AR214519A1 (en:Method) |
| AU (1) | AU506031B2 (en:Method) |
| CA (1) | CA1072960A (en:Method) |
| CH (1) | CH622795A5 (en:Method) |
| DD (1) | DD129791A5 (en:Method) |
| DE (1) | DE2716190A1 (en:Method) |
| DK (1) | DK143703C (en:Method) |
| FI (2) | FI63404C (en:Method) |
| GB (1) | GB1543283A (en:Method) |
| GR (1) | GR63658B (en:Method) |
| IE (1) | IE44989B1 (en:Method) |
| IL (1) | IL51853A (en:Method) |
| LU (1) | LU77100A1 (en:Method) |
| MT (1) | MTP811B (en:Method) |
| MX (1) | MX5340E (en:Method) |
| NO (1) | NO146777C (en:Method) |
| NZ (1) | NZ183846A (en:Method) |
| PL (1) | PL197373A1 (en:Method) |
| PT (1) | PT66428B (en:Method) |
| SE (2) | SE432932B (en:Method) |
| SU (1) | SU655314A3 (en:Method) |
| YU (1) | YU94877A (en:Method) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5337696A (en) * | 1976-08-26 | 1978-04-06 | Omnium Chimique Sa | Hexahydrocantinonee6 derivative |
| US4228168A (en) * | 1978-11-22 | 1980-10-14 | Tanabe Seiyaku Co., Ltd. | Azepino [1,2,3-lm]-β-carboline compounds and pharmaceutical composition thereof |
| US4367230A (en) * | 1980-01-04 | 1983-01-04 | Tanabe Seiyaku Co., Ltd. | Novel triazafluoranthene compound and processes for preparing the same |
| FR2494693A1 (fr) * | 1980-11-21 | 1982-05-28 | Synthelabo | Derives de l'hexahydro-2,3,3a,4,5,6 1h-indolo(3,2,1-de)(naphtyridine-1,5), leur preparation et leur application en therapeutique |
| FR2517679A1 (fr) * | 1981-12-03 | 1983-06-10 | Synthelabo | Derives de diaza-3,7a cyclohepta (j,k) fluorenes, leur preparation et leur application en therapeutique |
| LU84664A1 (fr) * | 1983-02-25 | 1984-11-08 | Onmichem S A | Alkyl-4-indolonaphtyridines et leur application therapeutique |
| EP0347980A1 (en) * | 1988-06-20 | 1989-12-27 | Duphar International Research B.V | 8,9-Annelated beta-carbolines and 8,9-anelated-3,4-dihydro-beta-carbolines |
| CN103193776A (zh) * | 2013-04-16 | 2013-07-10 | 苏州维泰生物技术有限公司 | 一种具有抗肿瘤疗效的新型萘啶衍生物的合成方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3299078A (en) * | 1962-10-01 | 1967-01-17 | Smith Kline French Lab | Pyrido [3', 4': 4, 5] pyrrolo [3, 2, 1-hi] indoles and-[3, 2, 1-ij] quinolines |
| US3555018A (en) * | 1968-12-03 | 1971-01-12 | Ayerst Mckenna & Harrison | Thiazinopyridoindolone derivatives |
-
1977
- 1977-04-07 DD DD7700198314A patent/DD129791A5/xx unknown
- 1977-04-11 MT MT811A patent/MTP811B/xx unknown
- 1977-04-11 YU YU00948/77A patent/YU94877A/xx unknown
- 1977-04-11 US US05/786,557 patent/US4190657A/en not_active Expired - Lifetime
- 1977-04-11 JP JP52041904A patent/JPS5823877B2/ja not_active Expired
- 1977-04-11 IL IL51853A patent/IL51853A/xx unknown
- 1977-04-12 NO NO77771263A patent/NO146777C/no unknown
- 1977-04-12 PT PT66428A patent/PT66428B/pt unknown
- 1977-04-12 AU AU24189/77A patent/AU506031B2/en not_active Expired
- 1977-04-12 GB GB15165/77A patent/GB1543283A/en not_active Expired
- 1977-04-12 CA CA275,948A patent/CA1072960A/en not_active Expired
- 1977-04-12 LU LU77100A patent/LU77100A1/xx unknown
- 1977-04-12 MX MX775626U patent/MX5340E/es unknown
- 1977-04-12 CH CH450777A patent/CH622795A5/fr not_active IP Right Cessation
- 1977-04-12 DE DE19772716190 patent/DE2716190A1/de not_active Withdrawn
- 1977-04-12 SE SE7704172A patent/SE432932B/xx unknown
- 1977-04-12 AR AR267179A patent/AR214519A1/es active
- 1977-04-12 DK DK161377A patent/DK143703C/da not_active IP Right Cessation
- 1977-04-13 SU SU772470258A patent/SU655314A3/ru active
- 1977-04-13 NZ NZ183846A patent/NZ183846A/xx unknown
- 1977-04-13 GR GR53198A patent/GR63658B/el unknown
- 1977-04-13 FI FI771159A patent/FI63404C/fi not_active IP Right Cessation
- 1977-04-13 PL PL19737377A patent/PL197373A1/xx unknown
- 1977-04-13 FI FI803790A patent/FI803790A7/fi not_active Application Discontinuation
- 1977-04-13 IE IE758/77A patent/IE44989B1/en unknown
-
1982
- 1982-02-25 SE SE8201181A patent/SE8201181L/sv not_active Application Discontinuation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0172096B1 (fr) | Dérivés d'acylaminométhyl-3 imidazo[1,2-a]pyridines, leur préparation et leur application en thérapeutique | |
| JPH05507687A (ja) | キヌクリジン誘導体 | |
| JPS5921684A (ja) | ３−アミノキヌクリジン誘導体、該誘導体の製法及び該誘導体を用いた治療上用の薬剤 | |
| RU2659784C2 (ru) | Сложноэфирное хиральное соединение (n-замещенный имидазол)-карбоновой кислоты, содержащее простую эфирную боковую цепь, его получение и применение | |
| JP2003528096A (ja) | デカヒドロ−イソキノリン | |
| IE920449A1 (en) | Imidazopyridine PAF/H1 antagonists | |
| JPS5823877B2 (ja) | ナフチリジン誘導体およびその製造方法 | |
| JP2012515191A (ja) | Ｃｎｓ障害の治療に有用な新規なベンゾトリアゾール誘導体 | |
| DE69106902T2 (de) | Imidazopyridazine, ihre Herstellung und Verwendung. | |
| JP3164372B2 (ja) | 融合インドール及びキノキサリン誘導体、その製造および使用 | |
| JPH02167279A (ja) | アポビンカミン酸誘導体 | |
| FR2593818A1 (fr) | Derives d'acylaminomethyl-3 imidazo(1,2-a)pyridine, leur preparation et leur application en therapeutique | |
| JPS6031833B2 (ja) | 新規な２０，２１↓−ジノルエブルナメニン誘導体、その製造法及び製薬組成物 | |
| DE69514532T2 (de) | Indol-2,3-dione-3-oximderivate, ihre herstellung und verwendung | |
| CN109071392A (zh) | 苯环衍生物及其制备方法和在医药上的应用 | |
| JPH01186866A (ja) | 分割化アミノピロリジン神経防護剤 | |
| CH642967A5 (de) | Neue pyrimidoisochinolin-derivate, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate. | |
| EP0201085A2 (en) | 6-Phenyl-1,2,3,4,4a,5,6,10b-octahydrobenz(h) isoquinolines | |
| DE69802624T2 (de) | Tetrahydroimidazo[2,1-a]isochinolinderivate | |
| DE2629877C2 (en:Method) | ||
| JPH04368359A (ja) | カプサイシン誘導体又はその酸エステルを有効成分とする鎮痛剤、血管拡張剤 | |
| JPS5831352B2 (ja) | 新規なインド−ル誘導体、その製造方法及び医薬としての使用 | |
| DE60213043T2 (de) | Verfahren zur Herstellung von 2-(4-Alkyl-1-Piperazinyl)-Benzaldehyd und -Benzylidenyl-Derivaten durch Nucleophile Substitution von 2-Fluorobenzaldehyd mit 4-Alkyl-1-Piperazinen in Wasser als Lösungsmittel | |
| HU195214B (en) | Process for producing 12b-substituted-1-(hydroxymethyl)-octahydro-indolo /2,3-a/ quinolizine derivatives and pharmaceutical preparations comprising these compounds | |
| WO1996006091A1 (de) | Verwendung von substituierten 6-amino-4h-pyranen |